It is critical to determine how we age if we hope to optimize the wellbeing of individuals, particularly older adults who represent a growing proportion of the population. Traditionally, studying aging was equated with unalterable decline and the development of disease. Although it is uncertain if the primary effects of aging can be fully distinguished from the secondary effects of disease, recent research has identified that aging and disease are not synonymous, and subsequently that aging can be optimized. This has been most clearly demonstrated in animal models with genetic manipulation and caloric restriction. In these systems mortality rate has been the primary marker of aging, but for human studies in vivo markers of aging are needed. Few primary markers of aging have been validated in human population studies. Aging of the lens, as assessed using lens transparency, has been proposed as a reflection of aging because it is detectable in early to mid adulthood and can be distinguished from known diseases of the lens, including specific types of cataract. The goal of this epidemiologic study is to determine the association of lens transparency with measures of disease and measures of aging in a cohort of older women. These will include atherosclerosis, a marker of vascular disease, and fasting glucose and insulin, markers of metabolic dysfunction. Additionally, telomere length and interleukin-6, markers of cellular senescence and chronic inflammation, respectively, will represent underlying biological processes that contribute to aging across tissues. If lens transparency is strongly related to these factors, it will provide evidence that transparency reflects cardiovascular disease or diabetes, and/or biological processes underlying aging. Finally, we will examine if lens opacity is associated with physical or cognitive function, markers of performance that indicate organismal aging independent of disease. For this investigation, we will conduct a cross-sectional cohort study in participants of the Healthy Women Study (HWS), a community-based longitudinal cohort study that began in 1983-84 and was just refunded for a 4th examination of the determinants of risk factor changes among women during peri- and postmenopause. To capitalize on the wealth of information obtained in the HWS during the current study cycle, we will add a measure of lens transparency using Scheimpflug photography, which uses linear densitometry to provide a quantitative measure of transparency. Validating lens transparency as a primary marker of aging will allow future researchers to employ it as a benchmark in unraveling the aging process, potentially as a novel intermediate marker for human intervention studies. PUBLIC HEALTH RELEVANCE: With this research we aim to determine the association of lens transparency to measures of cardiovascular disease and diabetes, the leading chronic disease causes of morbidity and mortality in the world, and to leukocyte telomere length, interleukin-6, and markers of physical and cognitive function, which illustrate aging on molecular and whole organism levels. Our results will help validate lens transparency as a primary marker of aging, disease, both, or neither;this is important because few primary markers of aging exist and none are measured in vivo, like lens transparency, which thus has the potential to more accurately reflect aging. Determining whether lens transparency is a primary marker of aging will allow future researchers to employ it as a benchmark in unraveling the aging process and could serve as a standard against which to test indicators of and modulators of aging in the hopes of optimizing aging.